tbuckley/cabot-search huggingface dataset:
Genetic Predictors of Ibrutinib-related Cardiovascular Side Effects in Patients with Chronic Lymphocytic Leukemia
Authors: Issam S. Hamadeh, Jai N. Patel, Ryan Jacobs, Hang Zeng, Jiaxian He, Bei Hu, Tamara Kay Moyo, Amy Soni, Steven Park, Ed Copelan, Belinda Avalos, Alicia Hamilton, Nury Steuerwald, Nilanjan Ghosh
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Patients with chronic lymphocytic leukemia (CLL) treated with ibrutinib are at risk of developing cardiovascular side effects (CVSE). The molecular determinants of CVSEs have not been fully elucidated. We interrogated genetic polymorphisms in the Bruton tyrosine kinase (BTK) signaling pathway for their association with ibrutinib-related CVSEs. Experimental Design: We conducted a retrospective/prospective observational pharmacogenetic study of 50 patients with newly diagnosed or relapsed CLL who received ibrutinib at a starting daily dose of 420 mg for at least 6 months. CVSEs, primarily atrial fibrillation and hypertension, occurred in 10 patients (20%), of whom 4 discontinued therapy. DNA was isolated from buccal swabs of all 50 patients and genotyped for 40 SNPs in GATA4, SGK1, KCNQ1, KCNA4, NPPA, and SCN5A using a customized next-generation sequencing panel. Univariate and multivariate logistic regression analysis were performed to determine genetic and clinical factors associated with the incidence of ibrutinib-related CVSEs. Results: GATA4 rs804280 AA (P = 0.043), KCNQ1 rs163182 GG (P = 0.036), and KCNQ1 rs2237895 AA (P = 0.023) genotypes were univariately associated with ibrutinib-related CVSEs. On the basis of multivariate analysis, a high genetic risk score, defined as the presence of at least two of these genotypes, was associated with 11.5-fold increased odds of CVSEs (P = 0.019; 95% confidence interval, 1.79–119.73). Conclusions: Our findings suggest possible genetic determinants of ibrutinib-related CVSEs in CLL. If replicated in a larger study, pretreatment pharmacogenetic testing for GATA4 and KCNQ1 polymorphisms may be a useful clinical tool for personalizing treatment selection for CLL and/or instituting early risk mitigation strategies.
Economic Evaluation of Novel Models of Care for Patients With Acute Medical Problems
Authors: Orlanda Q. M. Goh, Xiaohui Xin, Wan Tin Lim, Michelle W. J. Tan, Juliana Y. L. Kan, Hartini Bte Osman, Wanyi Kee, Tse Yean Teo, Wee Boon Tan, Mei Ling Kang, Nicholas Graves
Journal: JAMA Network Open (2023)

Importance During COVID-19, Singapore simultaneously experienced a dengue outbreak, and acute hospitals were under pressure to lower bed occupancy rates. This led to new models of care to treat patients with acute, low-severity medical conditions either at home, in a hospital-at-home (HaH) model, or in a clinic-style setting sited at the emergency department in an ambulatory care team (ACT) model, but a reliable cost analysis for these models is lacking. Objective To compare personnel costs of HaH and ACT with inpatient care. Design, Setting, and Participants In this economic evaluation study, time-driven activity-based costing was used to compare the personnel cost of inpatient care with treating dengue via HaH and treating chest pain via ACT. Participants were patients with nonsevere dengue and chest pain unrelated to a coronary event admitted via the emergency department to the internal medicine service of a tertiary hospital in Singapore. Exposures HaH for dengue and ACT for chest pain. Main Outcomes and Measures A process map was created for the patient journey for a typical patient with each condition. The amount of time personnel spent on delivering care was estimated and the cost per minute determined based on their wages in 2022. The total cost of care was calculated by multiplying the time spent by the per-minute cost of the personnel resource and summing all costs. Results Compared with inpatient care, HaH used 50% less nursing time (418 minutes, 95% uncertainty interval [UI], 370 to 465 minutes) but 80% more medical time (303 minutes, 95% UI, 270 to 338 minutes) per case of dengue. If implemented nationally, HaH would save an estimated 56 828 SGD per year (95% UI, −169 497 to 281 412 SGD [US $41 856; 95% UI, −$124 839 to $207 268]). The probability that HaH is cost saving was 69.2%. Compared with inpatient care, ACT used 15% less nursing time (296 minutes, 95% UI, 257 to 335 minutes) and 50% less medical time (57 minutes, 95% UI, 46 to 69 minutes) per case of chest pain. If implemented nationally, ACT would save an estimated 1 561 185 SGD per year (95% UI, 1 040 666 to 2 086 518 SGD [US $1 149 862; 95% UI, $766 483 to $1 536 786]). The probability that ACT is cost saving was 100%. Conclusions and Relevance This economic evaluation found that the HaH and ACT models decreased the overall personnel cost of care. Reorganizing hospital resources may help hospitals reap the benefits of reduced hospital-acquired infections, improved patient recovery, and reduced hospital bed occupancy rates.
The value of total caudate lobe resection for hilar cholangiocarcinoma: a systematic review
Authors: Da Wang, Fei Xiong, Guanhua Wu, Qi Wang, Junsheng Chen, Wenzheng Liu, Bing Wang, Yongjun Chen
Journal: International Journal of Surgery (2023)

Hilar cholangiocarcinoma is widely considered to have poor prognosis. In particular, combined caudate lobe resection (CLR) as a strategy for radical resection in hilar cholangiocarcinoma is important for improving the R0 resection rate. However, the criteria for R0 resection, necessity of CLR, optimal extent of hepatic resection, and surgical approach are still controversial. This review aimed to summarize the findings and discuss the controversies surrounding caudate lobe resection. Numerous clinical studies have shown that combined CLR treatment for hilar cholangiocarcinoma improves the R0 resection rate and postoperative survival time. Whether surgery for Bismuth type I or II is combined with CLR depends on the pathological type. Considering the anatomical factors, total rather than partial caudate lobe resection is recommended to achieve a higher R0 resection rate. In the resection of hilar cholangiocarcinoma, a proximal ductal margin ≥ 10 mm should be achieved to obtain a survival benefit. Although there is no obvious boundary between the right side (especially the paracaval portion) and right posterior lobe of the liver, Peng’s resection line can serve as a reference marker for right-sided resection. Laparoscopic resection of the caudate lobe may be safer, more convenient, accurate, and minimally invasive than open surgery, but it needs to be completed by experienced laparoscopic doctors.
Season of Conception and Risk of Cerebral Palsy
Authors: Haoran Zhuo, Beate Ritz, Joshua L. Warren, Zeyan Liew
Journal: JAMA Network Open (2023)

Importance Cerebral palsy (CP) is the most prevalent neuromotor disability in childhood, but for most cases the etiology remains unexplained. Seasonal variation in the conception of CP may provide clues for their potential etiological risk factors that vary across seasons. Objective To evaluate whether the month or season of conception is associated with CP occurrence. Design, Setting, and Participants This statewide cohort study examined more than 4 million live births that were registered in the California birth records during 2007 to 2015 and were linked to CP diagnostic records (up to year 2021). Statistical analyses were conducted between March 2022 and January 2023. Exposures The month and season of conception were estimated based on the child’s date of birth and the length of gestation recorded in the California birth records. Main Outcomes and Measures CP status was ascertained from the diagnostic records obtained from the Department of Developmental Services in California. Poisson regression was used to estimate the relative risk (RR) and 95% CI for CP according to the month or the season of conception, adjusting for maternal- and neighborhood-level factors. Stratified analyses were conducted by child’s sex and neighborhood social vulnerability measures, and the mediating role of preterm birth was evaluated. Results Records of 4 468 109 children (51.2% male; maternal age: 28.3% aged 19 to 25 years, 27.5% aged 26 to 30 years; maternal race and ethnicity: 5.6% African American or Black, 13.5% Asian, 49.8% Hispanic or Latinx of any race, and 28.3% non-Hispanic White) and 4697 with CP (55.1% male; maternal age: 28.3% aged 19 to 25 years, 26.0% aged 26 to 30 years; maternal race and ethnicity: 8.3% African American or Black, 8.6% Asian, 54.3% Hispanic or Latinx of any race, and 25.8% non-Hispanic White) were analyzed. Children conceived in winter (January to March) or spring (April to June) were associated with a 9% to 10% increased risk of CP (winter: RR, 1.09 [95% CI, 1.01-1.19]; spring: RR, 1.10 [95% CI, 1.02-1.20]) compared with summer (July to September) conceptions. Analyses for specific months showed similar results with children conceived in January, February, and May being at higher risk of CP. The associations were slightly stronger for mothers who lived in neighborhoods with a high social vulnerability index, but no child sex differences were observed. Only a small portion of the estimated association was mediated through preterm birth. Conclusions and Relevance In this cohort study in California, children conceived in winter and spring had a small increase in CP risk. These findings suggest that seasonally varying environmental factors should be considered in the etiological research of CP.
Harnessing Dendritic Cells: Next Frontier for Durable Immune Control in Myeloma
Authors: Madhav V. Dhodapkar
Journal: Clinical Cancer Research (2023)

Summary Immune-based approaches including T-cell redirection have transformed the therapeutic landscape in myeloma. Injection of dendritic cells (DC) led to the induction of immune responses in vaccinated patients with myeloma. These studies pave the way for future combination strategies harnessing DCs to enhance tumor immunity and improve outcomes in myeloma. See related article by Freeman et al., p. 4575
The impact of intensified staging and combined therapies in locally advanced pancreatic cancer: a secondary analysis of prospective studies
Authors: Michele Fiore, Gian Marco Petrianni, Pasquale Trecca, Gabriele D’Ercole, Alessandro Coppola, Vincenzo La Vaccara, Silvia Taralli, Paola Cimini, Carlo Greco, Edy Ippolito, Maria Lucia Calcagni, Bruno Beomonte Zobel, Damiano Caputo, Roberto Coppola, Sara Ramella, Rolando Maria D’Angelillo
Journal: International Journal of Surgery (2023)

To investigate the use of comprehensive pre-treatment staging with multiple diagnostic modalities, including functional imaging and minimally invasive surgical procedures, in locally advanced pancreatic cancer (LAPC) patients. The primary objective was to detect occult metastatic disease using staging laparoscopy and 18FFDG-PET/CT scan. The study also evaluated treatment efficacy and outcomes in LAPC patients treated with combined therapies.
A commentary on “Timing of surgery for aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis”
Authors: Min Song, Zhipeng Zhu, Jianxun Ren, Lirong Liang, Min Chen
Journal: International Journal of Surgery (2023)

Song, Min MD; Zhu, Zhipeng MD; Ren, Jianxun MD; Liang, Lirong MD; Chen, Min PhD Author Information
Delivery of short chain fatty acid butyrate to overcome Fusobacterium nucleatum-induced chemoresistance
Authors: Linfu Chen, Rui Zhao, Zheyu Kang, Zhiqin Cao, Nanhui Liu, Jingjing Shen, Cheng Wang, Feng Pan, Xiao Zhou, Zhuang Liu, Yang Yang, Qian Chen
Journal: Journal of Controlled Release (2023)
Differences in directives to limit treatment and discontinue mechanical ventilation between elderly and very elderly patients: a substudy of a multinational observational study
Authors: Karen E A Burns, Deborah J Cook, Keying Xu, Peter Dodek, Jesús Villar, Andrew Jones, Farhad N Kapadia, David J Gattas, Scott K Epstein, Paolo Pelosi, Kallirroi Kefala, Maureen O Meade, Leena Rizvi
Journal: Intensive Care Medicine (2023)
Survivin Dendritic Cell Vaccine Safely Induces Immune Responses and Is Associated with Durable Disease Control after Autologous Transplant in Patients with Myeloma
Authors: Ciara L. Freeman, Reginald Atkins, Indumathy Varadarajan, Meghan Menges, Jeffrey Edelman, Rachid Baz, Jason Brayer, Omar Castaneda Puglianini, Jose Leonel Ochoa-Bayona, Taiga Nishihori, Kenneth H. Shain, Bijal Shah, Dung Tsa Chen, Linda Kelley, Domenico Coppola, Melissa Alsina, Scott Antonia, Claudio Anasetti, Frederick L. Locke
Journal: Clinical Cancer Research (2023)

Abstract Purpose: We investigated whether a dendritic cell (DC) vaccine transduced with an adenoviral vector encoded with full-length survivin (Ad-S), with mutations neutralizing its antiapoptotic function, could safely generate an immune response and deepen clinical responses when administered before and after autologous stem cell transplant (ASCT) for multiple myeloma. Patients and Methods: This phase I first-in-human trial (NCT02851056) evaluated the safety of DC:Ad-S in newly diagnosed multiple myeloma not having achieved complete response with induction, given 7 to 30 days prior to stem cell collection and 20 to 34 days after ASCT. Anti-survivin antibodies and CD4+ and CD8+ specific T cells were quantified. Results: A total of 14 patients were treated and 13 included in the primary efficacy analysis. No serious adverse events were attributed to DC:Ad-S vaccine. Detectable anti-survivin antibodies increased from baseline in 9 of 13 (69%) patients, and 11 of 13 (85%) mounted either a cellular or humoral immune response to survivin. Seven patients had an improved clinical response at day +90, all of whom had mounted an immune response, and 6 of 7 patients remain event-free at a median follow-up of 4.2 years. Estimated progression-free survival at 4 years is 71% (95% confidence interval, 41–88). Conclusions: Two doses of DC:Ad-S, one given immediately before and another after ASCT, were feasible and safe. A high frequency of vaccine-specific immune responses was seen in combination with durable clinical outcomes, supporting ongoing investigation into the potential of this approach. See related commentary by Dhodapkar, p. 4524
Lateral augmentation of the jaw by the split expansion ridge technique. A critical review
Authors: Zvi Artzi
Journal: Periodontology 2000 (2023)

Abstract Bone augmentation has become a routine procedure to enhance and/or repair a deficient or resorbed alveolar ridge for predictable and successful implant placement. The split expansion ridge i.e., the alveolar ridge splitting (ARS) procedure, is one of the less invasive procedures, and is characterized by minor morbidity. This would allow to widen narrow ridges in order to allow implant reconstruction in a sufficient bone volume. Its efficacy and long‐term stability rely upon clinical opinions and long‐term retrospective studies, while prospective comparative studies and randomized controlled trials are rare. This critical review presents the development of this technique, describes the surgical procedure, and provides technical notes and modifications. The learning curve and in‐depth knowledge of the oral anatomy, as well as the recognition of incidence and management of complications are of utmost importance in the clinical application of the ARS procedure.
Revolutionizing pediatric orthopedics: GPT-4, a groundbreaking innovation or just a fleeting trend?
Authors: Shaoting Luo, Linfang Deng, Yufan Chen, Weizheng Zhou, Federico Canavese, Lianyong Li
Journal: International Journal of Surgery (2023)

Luo, Shaoting; Deng, Linfang; Chen, Yufan; Zhou, Weizheng; Canavese, Federico; Li, Lianyong MD, PhD Author Information
Vulnerability of Older Adults to Government Impersonation Scams
Authors: Lei Yu, Gary Mottola, Christine N. Kieffer, Robert Mascio, Olivia Valdes, David A. Bennett, Patricia A. Boyle
Journal: JAMA Network Open (2023)

Financial fraud and scams targeting older adults are on the rise and pose serious public health and economic threats. Research on the vulnerability of older adults to fraud and scams relies almost exclusively on self-reported data, which have several intrinsic limitations. Thus, how older adults truly respond to fraud attempts remains unclear.To explore the vulnerability of older adults to a US government impersonation scam.This cross-sectional study, conducted from October to December 2021 among communities in the greater Chicago metropolitan area, was framed as a fictitious government agency reaching out to older adults about a potential compromise of personal information relevant to their Social Security and Medicare benefits. Participants were older adults participating in the Rush Memory and Aging Project, an ongoing cohort study of chronic conditions of aging. Data analysis was performed from February to August 2023.Participants were exposed to deceptive materials through mailers, emails, and phone calls by a live agent.Based on the phone call data, participants were classified into 3 groups: no engagement (participants who did not answer the phone or call in), engagement (those who answered or called in but were skeptical about the legitimacy of the outreach and did not give away personal information), and conversion (participants who answered or called in without skepticism, or confirmed that they did not change their personal information, or provided the last 4 digits of their Social Security number).A total of 644 older adults (501 [77.8%] female, 143 [22.2%] male), with a mean (SD) age of 85.6 (7.5) years, were included. A total of 441 (68.5%) participants did not engage, 97 (15.1%) engaged but raised skepticism, and 106 (16.4%) converted. Older adults who engaged but with skepticism had the highest cognition and financial literacy, while those in the conversion group had the lowest scam awareness. No differences were observed in psychological and other behavioral measures by the levels of engagement.In this cross-sectional study using a behavioral experiment that mimicked a real-world imposter scam, a sizable number of older adults engaged without skepticism. Results suggest that many older adults, including those without cognitive impairment, are vulnerable to fraud and scams.
Treatment of Ovarian Cancer Beyond PARP Inhibition: Current and Future Options
Authors: Vikas Garg, Amit M Oza
Journal: Drugs (2023)

Ovarian cancer is the leading cause of gynecological cancer death. Improved understanding of the biologic pathways and introduction of poly (ADP-ribose) polymerase inhibitors (PARPi) during the last decade have changed the treatment landscape. This has improved outcomes, but unfortunately half the women with ovarian cancer still succumb to the disease within 5 years of diagnosis. Pathways of resistance to PARPi and chemotherapy have been studied extensively, but there is an unmet need to overcome treatment failure and improve outcome. Major mechanisms of PARPi resistance include restoration of homologous recombination repair activity, alteration of PARP function, stabilization of the replication fork, drug efflux, and activation of alternate pathways. These resistant mechanisms can be targeted to sensitize the resistant ovarian cancer cells either by rechallenging with PARPi, overcoming resistance mechanism or bypassing resistance pathways. Augmenting the PARPi activity by combining it with other targets in the DNA damage response pathway, antiangiogenic agents and immune checkpoint inhibitors can potentially overcome the resistance mechanisms. Methods to bypass resistance include targeting non-cross-resistant pathways acting independent of homologous recombination repair (HRR), modulating tumour microenvironment, and enhancing drug delivery systems such as antibody drug conjugates. In this review, we will discuss the first-line management of ovarian cancer, resistance mechanisms and potential strategies to overcome these.
A comment on ‘Preoperative dexamethasone administration in hepatectomy of 25-minute intermittent Pringle’s maneuver for hepatocellular carcinoma: a randomized controlled trial’
Authors: Hong Zhu, Xiaoping Wei
Journal: International Journal of Surgery (2023)

Department of HPB surgery, the second affiliated hospital of Kunming Medical University, Kunming, Yunnan, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of HPB surgery The second affiliated hospital of Kunming Medical University 374 Burma Road, Kunming, Yunnan,China, 650101 Fax:86 87165351281 Phone: 86 13888990023. E-mail address: [email protected] (X. Wei). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0/
Oral squamous cell carcinomas: state of the field and emerging directions
Authors: Yunhan Tan, Zhihan Wang, Mengtong Xu, Bowen Li, Zhao Huang, Siyuan Qin, Edouard C. Nice, Jing Tang, Canhua Huang
Journal: International Journal of Oral Science (2023)

Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.